Bristow M R, Gilbert E M, Abraham W T, Adams K F, Fowler M B, Hershberger R E, Kubo S H, Narahara K A, Ingersoll H, Krueger S, Young S, Shusterman N
Division of Cardiology, University of Colorado HSC, Denver 80262, USA.
Circulation. 1996 Dec 1;94(11):2807-16. doi: 10.1161/01.cir.94.11.2807.
We conducted a multicenter, placebo-controlled trial designed to establish the efficacy and safety of carvedilol, a "third-generation" beta -blocking agent with vasodilator properties, in chronic heart failure.
Three hundred forty-five subjects with mild to moderate, stable chronic heart failure were randomized to receive treatment with placebo, 6.25 mg BID carvedilol (low-dose group), 12.5 mg BID carvedilol (medium-dose group), or 25 mg BID carvedilol (high-dose group). After a 2- to 4-week up-titration period, subjects remained on study medication for a period of 6 months. The primary efficacy parameter was submaximal exercise measured by two different techniques, the 6-minute corridor walk test and the 9-minute self-powered treadmill test. Carvedilol had no detectable effect on submaximal exercise as measured by either technique. However, carvedilol was associated with dose-related improvements in LV function (by 5, 6, and 8 ejection fraction [EF] units in the low-, medium-, and high-dose carvedilol groups, respectively, compared with 2 EF units with placebo, P < .001 for linear dose response) and survival (respective crude mortality rates of 6.0%, 6.7%, and 1.1% with increasing doses of carvedilol compared with 15.5% in the placebo group, P < .001). When the three carvedilol groups were combined, the all-cause actuarial mortality risk was lowered by 73% in carvedilol-treated subjects (P < .001). Carvedilol also lowered the hospitalization rate (by 58% to 64%, P = .01) and was generally well tolerated.
In subjects with mild to moderate heart failure from systolic dysfunction, carvedilol produced dose-related improvements in LV function and dose-related reductions in mortality and hospitalization rate.
我们开展了一项多中心、安慰剂对照试验，旨在确定具有血管舒张特性的“第三代”β受体阻滞剂卡维地洛在慢性心力衰竭中的疗效和安全性。
345例轻度至中度稳定型慢性心力衰竭患者被随机分为四组，分别接受安慰剂治疗、每日两次服用6.25mg卡维地洛（低剂量组）、每日两次服用12.5mg卡维地洛（中剂量组）或每日两次服用25mg卡维地洛（高剂量组）。在2至4周的剂量递增期后，受试者持续服用研究药物6个月。主要疗效参数是通过两种不同技术测量的次极量运动，即6分钟走廊步行试验和9分钟自行驱动跑步机试验。两种技术测量的结果均显示，卡维地洛对次极量运动无明显影响。然而，卡维地洛与左心室功能的剂量相关改善有关（低、中、高剂量卡维地洛组的射血分数[EF]分别提高5、6和8个单位，而安慰剂组提高2个单位，线性剂量反应的P<0.001）以及生存率提高（卡维地洛剂量增加时，粗死亡率分别为6.0%、6.7%和1.1%，而安慰剂组为15.5%，P<0.001）。当将三个卡维地洛组合并时，接受卡维地洛治疗的受试者全因精算死亡风险降低了73%（P<0.001）。卡维地洛还降低了住院率（降低58%至64%，P = 0.01），并且总体耐受性良好。
在收缩功能障碍所致轻度至中度心力衰竭患者中，卡维地洛可使左心室功能得到剂量相关改善，并使死亡率和住院率呈剂量相关降低。
